The Art of Chemistry

To the science of chemistry
In the pursuit of truth
To the art of chemistry
For the welfare of man
To the teaching of youth
In a science
Ministrant of sciences

(quote from the Baker Hall, the home of chemistry, at Cornell University)

It is often difficult to write about science because it moves so fast. Often, a breakthrough one day will be overshadowed by a new story the next. This momentum is important and drives progress. I hope that this blog lets me calm my imagination and put in context some of the things that are in the science air.

Aspirin (pictured on the right) is a wonder drug. It stops headaches, improves outcomes from heart attacks and now can decrease the rate of colon cancer. In a story published last week, 500 people with Lynch syndrome were given aspirin and 500 more were not. Lynch syndrome predisposes one to colon cancer, and in the group taking aspirin the rates of colon cancer decreased.

Despite all the benefit, aspirin would not pass through the intensive drug approval process today. The effect of aspirin is achieved by inhibition of an enzyme called cyclooxygenase (COX) which itself leads to the synthesis of prostaglandins (PG). While inhibition of COX has many positive outcomes it also decreases a specific PG which is responsible for limiting the effect of hydrochloric acid in the stomach. This side effect leads to internal bleeding and would most likely cause a discontinuation of a clinical trial.

Hippocrates used bark from the willow tree as a pain reliever around 500 B.C. The active ingredient was salicylic acid (shown right). This compound was an even worse irritant to the stomach than aspirin. Felix Hoffman added an acetyl group to salicylic acid in 1897 and aspirin was born. We are lucky that a compound like this was discovered in tree bark and also that a scientist came along early enough to push through a drug that now is taken by over 100 million people.

A question lingers, though. Are there compounds currently that are failing safety profiles that could have, one day, the positive contribution of aspirin?

A joke at every end:
What animal do you not want to play cards with?
A cheetah.

Bacteria

I didn't even think of this one and I think about germs a lot. A research team in Colorado has shown that there are bacteria present on our shower heads that could negatively affect those with compromised immunities. This study examined 45 showers in hotels and random houses in various cities. Specifically, the researchers found 100 times more mycobacterium avium, a gram positive mycobacteria, shown on the right, in the water coming out of the shower head than in the water coming into it. Bacteria are classified based on a couple of characteristics, including their ability to absorb a stain called Crystal Violet. The majority of harmful bacteria can not retain this purple stain and are called gram negative. Those in good health should not worry about this germ filled study but those already sick should stick with metal shower heads, as they are less likely to breed bacteria than.

Now bacteria are not all bad. Professor van der Donk at the University of Illinois at Urbana-Champagne is using these tiny organisms to search for compounds that can kill other bacteria. This seems counter intuitive, why would bacteria make antibiotics? Indeed a gram positive bacteria, Lactococcus, is one of many bacteria that produce bacteriocins or toxins that inhibit the growth of similar bacteria. It seems it might help to be the only bully on the block. This is great for us because we can use these bacteria to identify new compounds that are medicinally relevant and most importantly have very creative structures. Nisin, shown on the right, is made by an enzyme in Lactococcus in two steps. While humans have been able to make Nisin in the lab in something like 70 steps. The neat thing about this molecule is that it has been used as an antibacterial in processed food for over 40 years. No resistance has been seen. This is amazing considering the amount of bacterial resistance that we are dealing with in the medical community. Currenlty, the researchers are exploring the relevant chemistry of this compound in order to understand how to make better antibiotics and also to perhaps harness some of these bacterias to make these antibiotics for us.

A joke at every end:

A man is pulled over for driving all over the road.
The cop, suspecting the driver of drinking, walks up to him and says "sir you are going to have to take a breathalyzer test."
"I can't do that," the man responds, "I have asthma and I might start coughing and die."
"Well we have an urine testing kit to measure alcohol level in the back," says the cop."So why don't you pee in a cup for me."
The man says, "I can't do that. I am a diabetic and if I pee I will lose too much sugar, faint, and die."
The cop says, "well then you are gonna have to go the station so we can draw some blood."
The man responds, "well I definitely can't do that. I am a hemophiliac and if I give blood I'll bleed everywhere and die."
"Fine" the cop says, "just get out of the car and walk in a straight line for me."
"I can't do that either," says the man.
"And why the hell not," asks the cop.
"Cause I am drunk," says the man.

Lab is a unicorn

Being a Teaching Assistant is exhilarating and terrifying at the same time. I led my first experimental organic lab this week. It went as well as a first of anything can go. At one point we had 15 steam baths going, none in the hood. My boss walked in and said "Yevgeniy, it's like a sauna in here!" Then he claimed I was putting the students on a steam diet. I am going to a wedding so maybe I was. Next time, we will use hot plates. I might have scared the students with an explosion story that happened when I was in college. A lab partner heated some ether on a hot plate. The ether boiled onto the hot plate, and we are lucky that no one got hurt.

The first lab's goal was to recrystallize benzoic acid (left) in order to separate it from salicylic acid (right). This is a nice starting lab as it reinforces a couple of important concepts and lets one use a lot of different equipment. In fact, the process of recrystallization is often utilized by the pharmaceutical industry to insure purity of their active pharmaceutical ingredient (the key to the pills in our medicine cabinet). The idea behind recrystallization is the following:
more molecules of a certain type (the one to the left or right) dissolve in a hot solvent then in a cold one. If you dissolve a contaminated mix of stuff in as little hot solvent as possible, when the solution is cooled (and the solvent can longer contain the same number of molecules as before) the least soluble compound will crystallize out of solution. If two compounds have very different solubilities this process makes sense.

What happens if two compounds have very similar solubilities? Turns out, if one of the compounds dominates the contaminated mix then when the saturated solution is cooled, the dominant compound will form pure crystals. In chemistry like tends to aggregate with like.

Benzoic acid was an excellent choice for the lab as it is a medically relevant compound, a treatment for various fungal skin diseases.

Did you know that DNA methylation causes DNA condensation and transcriptional silencing. Turns out that adding a carbon with three hydrogens to a base (usually cytosine - as shown on the right, note the extra CH3 group in the second cytosine - or guanisine) blocks RNA polymerase from making RNA. This kind of modification is responsible for the silencing of one out of two X chromosomes in female mammals and what makes calico cats so crazy (see for yourself). The hair pattern is a result of random x-inactivation - all because of a carbon and three hydrogen.

A joke at every end:

What do you get when you cross an insomniac, an agnostic, and a dyslexic?
Someone who lies awake all night long wondering if there really is a Dog.